HCA Data Explorer

Pathogen-induced tissue-resident memory T <sub>H</sub> 17 (T <sub>RM</sub> 17) cells amplify autoimmune kidney disease

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Updated June 19, 2024

Although it is well established that microbial infections predispose to autoimmune diseases, the underlying mechanisms remain poorly understood. After infection, tissue-resident memory T (TRM) cells persist in peripheral organs and provide immune protection against reinfection. However, whether TRM cells participate in responses unrelated to the primary infection, such as autoimmune inflammation, is unknown. By using high-dimensional single-cell analysis, we identified CD4+ TRM cells with a TH17 signature (termed TRM17 cells) in kidneys of patients with ANCA-associated glomerulonephritis. Experimental models demonstrated that renal TRM17 cells were induced by pathogens infecting the kidney, such as Staphylococcus aureus, Candida albicans, and uropathogenic Escherichia coli, and persisted after the clearance of infections. Upon induction of experimental glomerulonephritis, these kidney TRM17 cells rapidly responded to local proinflammatory cytokines by producing IL-17A and thereby exacerbate renal pathology. Thus, our data show that pathogen-induced TRM17 cells have a previously unrecognized function in aggravating autoimmune disease.

Christian F KrebsUniversity Medical Center Hamburg-Eppendorfc.krebs@uke.de
Hans-Willi MittrückerUniversity Medical Center Hamburg-Eppendorfh.mittruecker@uke.de
Christian F Krebs1
Daniel Reimers1
Yu Zhao1
Hans-Joachim Paust1
Patricia Bartsch1
Sarah Nuñez2
Mariana V Rosemblatt3
Malte Hellmig1
Christoph Kilian1
Alina Borchers1
Leon U B Enk1
Michael Zinke1
Martina Becker1
Joanna Schmid1
Stefanie Klinge1
Milagros N Wong1
Victor G Puelles1
Constantin Schmidt1
Tabea Bertram1
Natascha Stumpf4
Elion Hoxha1
Catherine Meyer-Schwesinger1
Maja T Lindenmeyer1
Clemens D Cohen1
Michael Rink1
Christian Kurts4
Sören Franzenburg5
Friedrich Koch-Nolte1
Jan-Eric Turner1
Jan-Hendrik Riedel1
Samuel Huber1
Nicola Gagliani1
Tobias B Huber1
Thorsten Wiech3
Holger Rohde1
Maria Rosa Bono6
Stefan Bonn1
Ulf Panzer1
Hans-Willi Mittrücker1
1University Medical Center Hamburg-Eppendorf
2Fundacion Ciencia Vida
3Universidad San Sebastian
4Institutes of Molecular Medicine and Experimental Immunology (IMMEI); Rheinische Friedrich-Wilhelms-Universität
5Kiel University
6Universidad de Chile
Ida Zucchi

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/dc0b65b0-7713-46f0-a339-0b03ea786046

Supplementary links are provided by contributors and represent items such as additional data which can’t be hosted here; code that was used to analyze this data; or tools and visualizations associated with this specific dataset.

1.https://figshare.com/s/7912de1afc7fd5bbefd4
None

Analysis Portals

None

Project Label

PathogenInducedResidentMemory

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

2 anatomical entities

Organ Part

Unspecified

Selected Cell Types

2 cell types

Disease Status (Specimen)

2 disease statuses

Disease Status (Donor)

2 disease statuses

Development Stage

human adult stage

Library Construction Method

CITE-seq

Nucleic Acid Source

single cell

Paired End

false

Analysis Protocol

matrix_generation

File Format

2 file formats

Cell Count Estimate

32.6k

Donor Count

9
rds.gz4 file(s)xlsx1 file(s)